title: cGMP-dependent protein kinase (PKG) mediates the anticontractile capacity of perivascular adipose tissue.
abstract: OBJECTIVE
  The aim of this study was to investigate the role of cGMP-dependent protein kinase (PKG) in mediating the anticontractile function of perivascular adipose tissue (PVAT) and whether its activation can rescue PVAT activity which is lost in an experimental model of inflammation.
  
  
  RESULTS
  Contractile responses to norepinephrine were assessed using wire myography from small arterial segments obtained from PKG(-/-), PKG(+/+), adipo(-/-), and C57Bl6/J mice with and without PVAT during normal oxygenation and hypoxia. An anticontractile effect of PVAT was observed in control blood vessels. This was not present in arteries from PKG(-/-) or PKG(+/+) with inhibition of PKG signalling using DT-2/ODQ. Hypoxia-induced loss of PVAT function was rescued by ANP activation of PKG as there was no effect in blood vessels from PKG(-/-) mice or in the presence of DT-2. Solution transfer studies demonstrated that PKG was necessary for the normal paracrine effects of PVAT on smooth muscle and endothelium. PKG activation by atrial natriuretic peptide (ANP) did not restore the absent PVAT anticontractile capacity in arteries from adiponectin(-/-) mice; however, inhibition of PKG did not further abrogate this effect suggesting dysregulation of PKG signalling pathways in this model. The absence of PKG was associated with reduced adipocyte adiponectin expression.
  
  
  CONCLUSIONS
  PKG plays a key role in regulating normal PVAT function both in modulating anticontractile factor release from adipocytes as well as being essential for its downstream dilator function in arterial smooth muscle.
authors.affiliation: Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, 3rd Floor Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Withers
authors.forename: Laura
authors.initials: L
authors.lastname: Simpson
authors.forename: Sharif
authors.initials: S
authors.lastname: Fattah
authors.forename: Matthias E
authors.initials: ME
authors.lastname: Werner
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Heagerty
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000502:physiology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009213:Myography; D013482:Superoxide Dismutase / Q000378:metabolism; D014661:Vasoconstriction
chemical_list: D052242:Adiponectin; D009320:Atrial Natriuretic Factor; D013482:Superoxide Dismutase; D017869:Cyclic GMP-Dependent Protein Kinases
keywords: Adipocyte; Adiponectin; PKG; PVAT; Small arteries